Nitrous oxide (N2O) has robust mood-altering effects, serves as a reinforcer in animals and in some humans, and is abused by some humans. There are several important issues related to the interoceptive and reinforcing effects of N2O in humans which have yet to be explored, and thus, forms the basis of this application.. There are four series of experiments in the application. In the first series, we plan to train healthy volunteers to discriminate between a subanesthetic concentration of N2O and oxygen. Once the discrimination is learned (subjects emit one response while breathing N2O and emit a different response when inhaling oxygen), other general anesthetics at subanesthetic concentrations and sedatives will be tested in this procedure to determine if they share similar interoceptive (discriminative and subjective) effects with N2O. This series should complement those human drug discrimination studies already done with non-inhalant psychoactive drugs. In the second series of studies, the neurochemical events which mediate the subjective effects of N2O will be investigated via the use of opiate and benzodiazepine antagonist challenges. Naloxone and flumazenil will be administered during N2O inhalation to determine if the subjective and psychomotor effects induced by N2O are attenuated. In the third series, we will investigate several variables which may modulate the reinforcing effects of N2O, including drug history, the ability to regulate dose and duration of N2O exposure, instructions (information) regarding the effects of N2O, and presence/absence of stress in the context of N2O inhalation. Finally, in the fourth series, the degree to which acute tolerance develops to the subjective, psychomotor, and analgesic effects of N2O at difference concentrations will be examined. These studies should address several fundamental questions regarding the actions of N2O which may be related to its illicit use and its widespread acceptance (i.e., liking) amongst people undergoing dental/medical procedures.